Table 7.

Working Group integrated assessment of current practices and considerations for the inclusion of reproductive endpoints in general and juvenile toxicity studies for pharmaceutical drug development

Study Type	Species	Subset	Fertility Assessments	Clinical Pathology, Organ Weights, Macroscopic and Histopathologya	Record Reproductive Maturityb
General Toxicity (GenTox)	Rodent	Male	Sperm at necropsy and/or hormones for causec	Complete	Yes
		Female	Cycling (vaginal smears) and/or hormones for cause	Complete; record estrous cycle stage as needed to clarify or interpret results	Yes
	Dog	Male	Semen and/or hormones for cause	Complete	Yes
		Female	Rarely assessed	Complete; record estrous cycle stage if needed to clarify or interpret results	Yes
	NHP	Male	Semen and/or hormones for cause	Complete	Yes
		Female	Cycling (vaginal smears) for cause; hormones rare	Complete; record menstrual cycle stage if needed to clarify or interpret results	Yes
Juvenile	Rodent	Preweaning	Not applicable	Organ weights and clinical pathology rare; targeted histopathology (i.e. immune or nervous systems), typically after 6-8 weeks of age	Yes, both sexes
		Postweaning to mature	Sperm at necropsy and/or hormones for cause once mature; mating trials possible	Complete, typically after PND70	Yes, both sexes
	Dog	Immature	Not applicable	Complete, typically after 3-6 months	Yes, both sexes
	NHP	Immature	Not applicable	Complete; typically after 6-12 months	Yes, both sexes

^aComplete refers to clinical pathology, organ weight and anatomic pathology endpoints commonly included in general toxicity studies

^bRecording may be limited to reproductive immaturity, with reproductive maturity being the default as long as this is stated in the report

^c‘For cause’ indicates that these would only be added when prior data or pharmacology and mechanism suggest a potential effect